Skeletal Muscle Changes After CrtPhase 4NCT01019915
Effect of Cardiac Resynchronization Therapy (CRT) on Skeletal Muscle Histology, Neuroendocrine Activation and Inflammatory Response
A Phase 4 study testing CRT in people with Skeletal Muscle Changes After Crt, run by Helse Stavanger HF at 1 site in Norway.
Trial summary
Heart failure patients with left bundle branch block have a poor prognosis. Biventricular pacing which synchronize the heart pump action is associated with improved functional capacity. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Skeletal Muscle Changes After Crt
- What is being tested?
- CRT
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteNorway
- Study dates
- Jan 2004to Nov 2009
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Heart failure, left bundle branch block
Who cannot join
- serious comorbidity including systemic inflammatory disease
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Cardiac Resynchronization Therapy on Skeletal Muscle Histology, Neuroendocrine Activation and Inflammatory Response
Heart failure patients with left bundle branch block have a poor prognosis. Biventricular pacing which synchronize the heart pump action is associated with improved functional capacity. This study aims to evaluate the basic changes in skeletal muscle functioning after a period of biventricular pacing in 21 patients with heart failure.
Read the detailed description
Congestive heart failure (CHF) is the most common hospital discharge diagnosis in elderly patients . Fatigue and dyspnea with exercise intolerance and a poor quality of life are the main characteristics of this syndrome , and it is associated with substantial mortality and morbidity , .
Although the systolic dysfunction has been recognized as the primum movens of CHF, it is now generally accepted that the progression of the syndrome is not solely related to the pump failure.
The neuro-endocrine model has reached a wide consensus as one of the basic mechanisms for progressive heart failure based on the good results obtained by ACE-inhibitor therapy . A decade ago the cytokine model was added to explain the syndrome of heart failure . The cytokines are highly potent endogenous peptides produced by different cell types . Elevated levels might be markers for cardiac cachexia, but they may also play an important role in the mechanism of CHF progression . Subsequently, the muscle hypothesis was proposed as an explanation for the deconditioning in CHF patients . In skeletal muscle from healthy individuals there is a balanced distribution between type I fibres (aerobic), type IIA fibres (both aerobic and anaerobic) and type IIB fibres (mostly anaerobic). In CHF a shift to type II fibres and a reduced capillary density as well as a reduced cytochrome oxidase activity is observed, but the mechanisms leading to such a shift have not been clarified . Deconditioning may be an important factor aggravating the underlying pathophysiology in CHF and exercise training has been shown to improve exercise performance and to reduce symptoms in this population . This is partly mediated by activation of the Protein PGC-1, a critical factor coordinating the activation of metabolic genes required for substrate utilization and mitochondrial biogenesis . The increase in this enzyme has been highly correlated to increase in peak VO2 after a aerobic interval training program in heart failure .
One would expect that an improvement in exercise performance following improvement in central hemodynamics with cardiac resynchronization therapy (CRT) would be associated with improved muscular blood flow and energy metabolism. However, so far no reports have been published on the skeletal muscle response to CRT. The purpose of this study was to evaluate the effect of 6 months CRT pacing on skeletal muscle histology and mitochondrial mass and the association of these changes to alterations in functional capacity as measured with peak VO2. Moreover, we also sought to assess the relationship between changes in skeletal muscle and alterations in the inflammatory response in serum and in skeletal muscle.
- Conditions
- Skeletal Muscle Changes After Crt
- Being tested
- CRT
- Keywords
- CRT, heart failure, left bundle branch block, skeletal muscle, cytokines, VO2, pgc1alpha
- Medical subject headings
- Heart Failure, Bundle-Branch Block
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CRTDevice
Insertion of CRT in patients with left bundle branch block. Assessment of skeletal muscle and infalmmatory profile
| Study group | Role | What they receive |
|---|---|---|
| Heart failure patients. Intervention CRT | Other | CRT implantation in heart failure. Effect of intervention after 6 months of treatment. Receives: Device: CRT |
What is being measured
The primary outcome is the main question the study is designed to answer.
capillary density
To assess if CRT improves skeletal muscle cappillary density
Measured: finnished
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2009 (estimated)
- Study startJan 2004
- Primary completionNov 2009
- Study completionNov 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Skeletal Muscle Changes After CrtStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Helse Stavanger HF
- Sponsor type
- Other government
- Collaborators
- University of Tromso, University of Oslo, The Royal Norwegian Ministry of Health
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01019915
- Sponsor's protocol ID
- CRT-AIL-SUS 2009
- Status last verified
- Jun 2011
- First submitted
- 23 Nov 2009
- Last updated
- 28 Jul 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Larsen AI, Valborgland T, Ogne C, Lindal S, Halvorsen B, Munk PS, Kvaloy JT, Aukrust P, Yndestad A. Plasma tumour necrosis factor correlates with mRNA expression of tumour necrosis factor and mitochondrial transcription factors in skeletal muscle in patients with chronic heart failure treated with cardiac resynchronization therapy: potential role in myopathy. Eur J Prev Cardiol. 2020 Dec;27(19):2362-2366. doi: 10.1177/2047487319855796. Epub 2019 Jun 8. No abstract available.
PubMed 31389718Larsen AI, Lindal S, Myreng K, Ogne C, Kvaloy JT, Munk PS, Aukrust P, Yndestad A, Dickstein K, Nilsen DW. Cardiac resynchronization therapy improves minute ventilation/carbon dioxide production slope and skeletal muscle capillary density without reversal of skeletal muscle pathology or inflammation. Europace. 2013 Jun;15(6):857-64. doi: 10.1093/europace/eus428. Epub 2013 Jan 15.
PubMed 23322010
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Cardiac Resynchronization Therapy on Skeletal Muscle Histology, Neuroendocrine Activation and Inflammatory Response
- ClinicalTrials.gov ID
- NCT01019915
- Acronym / sponsor ID
- CRT-AIL-SUS 2009
- Conditions
- Skeletal Muscle Changes After Crt
- Keywords
- CRT, heart failure, left bundle branch block, skeletal muscle, cytokines, VO2, pgc1alpha
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Helse Stavanger HFOther government
- Collaborators
- University of Tromso, University of Oslo, The Royal Norwegian Ministry of Health
- Study start
- Jan 2004
- Primary completion
- Nov 2009 (actual)
- Study completion
- Nov 2009 (actual)
- First posted
- 25 Nov 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Heart failure patients with left bundle branch block have a poor prognosis. Biventricular pacing which synchronize the heart pump action is associated with improved functional capacity. This study aims to evaluate the basic changes in skeletal muscle functioning after a period of biventricular pacing in 21 patients with heart failure.
Detailed description
Congestive heart failure (CHF) is the most common hospital discharge diagnosis in elderly patients . Fatigue and dyspnea with exercise intolerance and a poor quality of life are the main characteristics of this syndrome , and it is associated with substantial mortality and morbidity , .
Although the systolic dysfunction has been recognized as the primum movens of CHF, it is now generally accepted that the progression of the syndrome is not solely related to the pump failure.
The neuro-endocrine model has reached a wide consensus as one of the basic mechanisms for progressive heart failure based on the good results obtained by ACE-inhibitor therapy . A decade ago the cytokine model was added to explain the syndrome of heart failure . The cytokines are highly potent endogenous peptides produced by different cell types . Elevated levels might be markers for cardiac cachexia, but they may also play an important role in the mechanism of CHF progression . Subsequently, the muscle hypothesis was proposed as an explanation for the deconditioning in CHF patients . In skeletal muscle from healthy individuals there is a balanced distribution between type I fibres (aerobic), type IIA fibres (both aerobic and anaerobic) and type IIB fibres (mostly anaerobic). In CHF a shift to type II fibres and a reduced capillary density as well as a reduced cytochrome oxidase activity is observed, but the mechanisms leading to such a shift have not been clarified . Deconditioning may be an important factor aggravating the underlying pathophysiology in CHF and exercise training has been shown to improve exercise performance and to reduce symptoms in this population . This is partly mediated by activation of the Protein PGC-1, a critical factor coordinating the activation of metabolic genes required for substrate utilization and mitochondrial biogenesis . The increase in this enzyme has been highly correlated to increase in peak VO2 after a aerobic interval training program in heart failure .
One would expect that an improvement in exercise performance following improvement in central hemodynamics with cardiac resynchronization therapy (CRT) would be associated with improved muscular blood flow and energy metabolism. However, so far no reports have been published on the skeletal muscle response to CRT. The purpose of this study was to evaluate the effect of 6 months CRT pacing on skeletal muscle histology and mitochondrial mass and the association of these changes to alterations in functional capacity as measured with peak VO2. Moreover, we also sought to assess the relationship between changes in skeletal muscle and alterations in the inflammatory response in serum and in skeletal muscle.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Heart failure patients. Intervention CRT | Other | Device: CRTCRT implantation in heart failure. Effect of intervention after 6 months of treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Heart failure, left bundle branch block
Key exclusion criteria (1 listed)
- serious comorbidity including systemic inflammatory disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CRTInsertion of CRT in patients with left bundle branch block. Assessment of skeletal muscle and infalmmatory profile | Device | Heart failure patients. Intervention CRT |
Primary outcome
capillary density
Time frame: finnished
To assess if CRT improves skeletal muscle cappillary density
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2015.
- Derived from this study: PubMed 31389718Larsen AI, Valborgland T, Ogne C, Lindal S, Halvorsen B, Munk PS, Kvaloy JT, Aukrust P, Yndestad A. Plasma tumour necrosis factor correlates with mRNA expression of tumour necrosis factor and mitochondrial transcription factors in skeletal muscle in patients with chronic heart failure treated with cardiac resynchronization therapy: potential role in myopathy. Eur J Prev Cardiol. 2020 Dec;27(19):2362-2366. doi: 10.1177/2047487319855796. Epub 2019 Jun 8. No abstract available.
- Derived from this study: PubMed 23322010Larsen AI, Lindal S, Myreng K, Ogne C, Kvaloy JT, Munk PS, Aukrust P, Yndestad A, Dickstein K, Nilsen DW. Cardiac resynchronization therapy improves minute ventilation/carbon dioxide production slope and skeletal muscle capillary density without reversal of skeletal muscle pathology or inflammation. Europace. 2013 Jun;15(6):857-64. doi: 10.1093/europace/eus428. Epub 2013 Jan 15.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing CRT in people with Skeletal Muscle Changes After Crt, run by Helse Stavanger HF at 1 site in Norway.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
capillary density (time frame: finnished). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01019915, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jul 2015.